Step-wise decline in 16S rRNA level was accompanied by reduction in the number of infected cells (1 and 20 μM mevastatin), as well as the appearance of “”aberrant”" chlamydial forms (20 μM mevastatin) until complete eradication of chlamydial growth takes place (40 μM mevastatin).

Euo mRNA level has been changing in a similar manner, except inconsistent increase seen at 20 μM concentration of mevastatin. However, it is known that euo mRNA can be highly induced when the developmental cycle of C. trachomatis in cultured cells is compromised by addition of cytokines and other substances https://www.selleckchem.com/products/mln-4924.html affecting chlamydial growth [28]. It has been proposed, that increased expression of euo may inhibit transcription of the genes specific for “”late phase”" of chlamydial developmental cycle [28, 29]. Thus, enhanced transcription rate of euo may represent self-sufficient mechanism predetermining anti-chlamydial activity of mevastatin. It is also important to conclude, that according to our results Selleck RG-7388 mevastatin has no effect on initial interaction of chlamydial particles

with host cell, allowing the entry of the pathogen into hepatocytes. Therefore we find more assume that later stages of chlamydial developmental cycle are affected by mevastatin treatment. The effect of different metabolites and inhibitors of mevalonate pathway needs to be tested in hepatocytes infected with C. trachomatis in presence of mevastatin. It is possible, that anti-chlamydial activity of mevastatin takes place due to reduced geranylgeranylation of host cell proteins as it happens in case of lovastatin-treated hepatocytes infected with hepatitis C virus [30]. Conclusions We have demonstrated that ongoing cholesterol synthesis is essential for chlamydial growth in hepatocytes. Although the precise mechanism of anti-chlamydial activity of mevastatin remains to be elucidated, RVX-208 targeting the cholesterol biosynthetic pathway may represent an effective strategy in management of chlamydial infection. Acknowledgements Ms Agni Roce is appreciated for invaluable help during experimental work and manuscript preparation. References

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